Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer (NCT05014776), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1).

2. Clinical Question

The study’s stated purpose was to evaluate safety and clinical activity of the four-drug regimen in patients with metastatic pancreatic adenocarcinoma who had progressed after prior chemotherapy. The clinical activity question is represented by objective response: whether a participant’s tumor measurements met the registry’s criteria for complete or partial response.

Because the design has one treatment group and no listed comparator, the record cannot support a randomized, between-group estimate of treatment effect. A response proportion, if reported, would describe outcomes among the analyzed participants in this group. It would not by itself distinguish the regimen’s contribution from other explanations for observed outcomes.

The registry identifies a secondary safety outcome concerning drug-related adverse events requiring treatment discontinuation. It also reports adverse-event summaries, including serious-event figures and deaths. These safety summaries are distinct from the primary response endpoint. The record does not report the response count, an objective response rate, or an inferential estimate of response precision.

3. Trial Design

This is a completed Phase 2 study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The registry lists a start date of 2022-08-22 and a primary completion date of 2024-04-03. Enrollment is recorded as 17. The study title names CRS-207, pembrolizumab, ipilimumab, and tadalafil in metastatic pancreatic cancer; the official title specifies previously treated metastatic pancreatic adenocarcinoma.

The design is recorded as single-group, with allocation listed as NA and masking as none. One arm is listed: tadalafil, pembrolizumab, ipilimumab, and CRS-207. No control arm is listed. Consequently, the study’s design is suited to describing outcomes observed in the treated group, but it does not provide a concurrent comparison for estimating differences between treatment strategies.

The primary endpoint is objective response rate using Response Evaluation Criteria for Solid Tumors, version 1.1 (RECIST 1.1), with a timeframe of 9 months. The endpoint counts participants with complete or partial response. The registry description classifies participants who discontinue because of toxicity or clinical progression before post-baseline tumor assessments as non-responders. Participants who discontinue for other reasons before their first study-drug dose are excluded from the analysis.

The listed secondary outcome is the number of participants experiencing drug-related adverse events requiring treatment discontinuation. The record is marked completed, but completion status does not itself convey whether the primary endpoint was met or what the results were. The registry record does not report the statistical analysis plan, the primary endpoint result, or an analysis population count.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1), measured over 9 months.

Objective response rate (ORR) is a binary endpoint: each participant is classified according to whether they achieved a complete or partial response under RECIST 1.1. The registry defines complete response as disappearance of all target lesions and partial response as a decrease of >30% in the sum of target-lesion diameters. The endpoint timeframe is 9 months.

Response is used in oncology studies as a direct measure of tumor change under prespecified criteria. It differs from outcomes that track how long participants live or how long they remain free of progression: ORR asks whether a qualifying response was recorded, rather than measuring duration. This is a general description of the endpoint concept, not a claim about results in this study.

The registry specifies how certain early discontinuations are classified. Participants stopping because of toxicity or clinical progression before post-baseline tumor assessment are treated as non-responders. Those stopping for other reasons before receiving their first study-drug dose are excluded from the analysis. These rules affect which participants contribute to the endpoint and how their response status is assigned.

The registry record does not report the number of participants with complete or partial response, the response rate, or a confidence interval. Therefore, the endpoint definition is available, but the observed primary result and its precision cannot be evaluated from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure. Each participant is classified as having achieved complete response, partial response, or neither according to RECIST 1.1; the registry defines responders as those achieving complete or partial response. A response proportion would ordinarily summarize the number classified as responders relative to the relevant analysis population. The registry record does not report that numerator, the analyzed denominator, or a resulting proportion.

What does a binary endpoint capture?

As a general statistical concept, a binary endpoint reduces a participant’s outcome to one of two categories for analysis, such as response versus no response. This can make the clinical question straightforward, but it also discards information about the degree of tumor change within each category and about when or how long a response lasts. Those other features are not the primary endpoint described in this record.

The registry’s classification rules matter. Participants who stop treatment because of toxicity or clinical progression before post-baseline tumor assessments are counted as non-responders. Participants who stop for other reasons before their first study-drug dose are excluded. These rules establish how some cases are handled, but the record does not say how many participants fell into either situation or provide a complete account of missing assessments.

What would an interval estimate tell readers?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a response proportion. A narrower interval indicates greater precision under the method’s assumptions; a wider interval indicates less precision. An interval does not guarantee that the true value lies within its bounds, nor does it remedy limitations in study design. No confidence interval for ORR is reported in the registry record, so the precision of the primary result cannot be assessed.

What does a single-group design allow?

With one treatment group, the analysis can describe the recorded outcomes in that group. It cannot estimate a randomized treatment-versus-control contrast because no concurrent comparator is listed. General comparisons with outcomes from other populations or studies would require information and assumptions not reported in this record. The registry’s allocation field is NA, and the design is identified as single-group rather than as a randomized comparison.

The study has no reported analyses in the registry record. No p value, adjusted or unadjusted estimate, or model-based result is reported for the primary endpoint. The record also does not report a statistical analysis plan, so the intended inferential methods, if any, cannot be characterized. A missing reported analysis is not evidence that an analysis was conducted with a particular method.

How should planning illustrations be read?

General sample-size calculations are planning tools, not summaries of observed outcomes. The stated planning convention describes hypothetical two-arm calculations using equal allocation, a two-sided significance level of 0.05, a normal approximation, and an effect defined as a stated fraction of the observed effect. It specifies participants per arm for 80% power for non-time-to-event outcomes. Such illustrations are not the trial’s own design or evidence of observed power. The registry record does not report a numerical planning result or a trial-specific sample-size justification.

Over-dispersion is a general concern when observed variability exceeds what a simple statistical model assumes; ignoring it can make uncertainty appear too small. That concept is not identified as a feature of this binary endpoint in the registry record, and no model or dispersion estimate is reported. Likewise, the record does not provide enough information to assess model assumptions or reproduce a primary analysis.

For safety, event counts and percentages are descriptive summaries. Their interpretation depends on what was counted, the population at risk, the observation period, event definitions, and attribution rules. The record gives at-risk and affected participant counts for broad adverse-event summaries and lists selected serious-event terms with percentages, but does not report all these contextual details. Consequently, those figures should be read as registry summaries rather than as adjusted comparisons or causal estimates.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-")
n      <- c(17)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-  17  0  0.0  0.0  19.5  0.0  18.4  0.1  18.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ORR as the primary outcome and drug-related adverse events requiring treatment discontinuation as a secondary outcome. It does not report a multiplicity strategy for handling inference across outcomes or any other analyses. Without such a strategy, the record does not establish how statistical error across multiple questions was intended to be controlled. No p values or inferential results are reported for evaluating that issue.

The record gives an endpoint rule for some participants without post-baseline tumor assessments: those who discontinue because of toxicity or clinical progression before assessment are classified as non-responders. Participants who discontinue for other reasons before their first study-drug dose are excluded from the analysis. The number of participants in either category is not reported in the registry record.

Other missing-data details are not reported in the registry record. This includes the number of participants with missing or unevaluable response assessments, the handling of missing assessments outside the stated discontinuation rules, and the primary endpoint analysis denominator. The record does not describe sensitivity analyses for missing outcomes.

The analysis populations are also not described beyond the endpoint’s stated exclusions and non-responder classification. The registry does not report whether all enrolled participants, all participants who received study drug, or another defined group formed the analysis population. The enrollment figure alone does not establish the primary endpoint denominator. These omissions limit assessment of the response estimate’s construction and of potential sensitivity to analysis choices.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (64.7%), abdominal pain (17.6%), biliary obstruction (11.8%), bowel obstruction (11.8%), stroke (11.8%).

The registry reports serious adverse events for the listed arm as 12 participants affected among 17 at risk. For other adverse events, it reports 17 affected among 17 at risk. It also reports 16 deaths. These are distinct summaries; the record does not specify a causal relationship between the regimen and each event or death. The death figure should not be read as a treatment-attributed count.

The listed serious-event terms are Disease Progression at 64.7%, Abdominal pain at 17.6%, Biliary Obstruction at 11.8%, Bowel Obstruction at 11.8%, Stroke at 11.8%, and Anemia at 5.9%. The registry presents these as serious-event terms. The figures are not estimates of risk relative to a comparator, because no concurrent comparator is listed.

Adverse-event percentages are descriptive and depend on the registry’s event definitions, observation period, and reporting conventions. Those details are not fully reported in the record. The listed terms should not be assumed to be mutually exclusive: a participant may contribute to more than one event category. The record does not provide enough information to infer how many individual participants experienced any particular combination of events.

These summaries support a description of reported safety events, not a causal conclusion about the four-drug regimen. The registry also identifies a secondary outcome concerning drug-related events requiring treatment discontinuation, but its result is not reported.

13. What the Result Does, and Does Not, Mean

The study addresses safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in previously treated metastatic pancreatic adenocarcinoma. Its primary endpoint is clearly defined as ORR under RECIST 1.1 over 9 months. The registry record does not report the response count or response rate, so it does not establish what objective response was observed in the study group.

The single-group design means that any observed outcome would be descriptive of the participants analyzed in that group. There is no randomized comparator in the record to show how outcomes differed under another treatment strategy. This limits causal interpretation and prevents a direct comparative estimate from this study design.

The adverse-event summaries provide information about reported safety events, including the number affected in broad categories, selected serious-event terms and percentages, and the death count. They do not, on their own, establish that treatment caused any event. The registry record does not report a comparator, detailed event attribution, or the context needed to interpret individual outcomes.

The record also does not report a confidence interval, p value, analysis population, or statistical analysis plan for the primary endpoint. Therefore, statistical precision and the inferential approach cannot be assessed. A completed study status indicates the registry’s recorded status, not that a result was positive, clinically meaningful, or statistically conclusive.

In short, the registry supports statements about the study’s design, endpoint definition, and listed safety summaries. It does not support a conclusion about the magnitude or precision of the primary response result, since that result is not reported. Nor does it support a treatment-versus-control conclusion or a causal safety claim.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a prespecified endpoint and a reported result. The registry defines ORR using RECIST 1.1 and describes how some early discontinuations are classified. Those details clarify what the primary outcome was intended to represent, but an endpoint definition alone does not reveal how many participants responded or how uncertain an estimate would be.

The single-group design also illustrates the limits of descriptive evidence. Outcomes in a treated group can be summarized, but without a concurrent comparator they do not estimate a randomized contrast. This distinction matters whenever readers encounter response or safety figures: a percentage describes a group under the stated conditions, whereas a comparative effect requires an appropriate comparison and analysis.

Safety summaries show why denominators and attribution matter. The registry records affected participants and at-risk participants for broad adverse-event categories, as well as selected serious-event terms and deaths. These quantities answer different descriptive questions from ORR. They should not be conflated with treatment-caused events or with a comparative safety estimate.

The missing analysis details are also relevant. The record does not report the primary result, uncertainty interval, analysis population, or statistical analysis plan. Without these, readers cannot assess precision, reproduce the primary analysis, or evaluate how missing assessments and other analysis choices may have influenced the result. This is a limitation of what is reported in the registry, not a claim about work that may or may not have occurred elsewhere.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important trial-specific limitation for interpreting efficacy is that the registry record does not report the primary ORR result. It gives the endpoint definition and timeframe but no response count, response rate, confidence interval, or p value. The response outcome therefore cannot be quantitatively interpreted from this record.

The single-group design has no concurrent comparator. Even if a response estimate were reported, this design would not provide a randomized comparison or isolate the effect of the regimen from other explanations. The record identifies masking as none and allocation as NA; no randomized allocation is listed.

The endpoint rules specify non-responder classification for participants who discontinue because of toxicity or clinical progression before post-baseline assessment, and exclusion for those who discontinue for other reasons before their first dose. However, the record does not report how many participants were affected by these rules, the primary analysis denominator, or broader missing-assessment details. This limits evaluation of how endpoint classification and missing data shaped the analysis.

The registry reports selected safety summaries but does not give full event-level context, complete attribution information, or a comparator. It also does not report the result for the secondary outcome concerning drug-related adverse events requiring treatment discontinuation. The reported death count is not accompanied by a cause or timing context in the record.

Finally, the registry record does not report the statistical analysis plan, multiplicity approach, or a trial-specific sample-size justification. These omissions prevent assessment of intended inferential procedures and planned precision. They should be understood as limits of the registry record, not as evidence that particular procedures were or were not used outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer — NCT05014776.
• Registry record last updated 2026-04-28; status last verified 2026-04.
• Results first posted 2025-01-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT05014776 is a completed Phase 2, single-group study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. It evaluated tadalafil, pembrolizumab, ipilimumab, and CRS-207 in previously treated metastatic pancreatic adenocarcinoma. The registry lists enrollment of 17, a start date of 2022-08-22, and a primary completion date of 2024-04-03.

The primary endpoint was ORR under RECIST 1.1 over 9 months. The registry describes response classification and rules for certain early discontinuations, but does not report the primary result or its statistical analysis. No concurrent comparator is listed.

Safety summaries include serious adverse events, other adverse events, selected serious-event terms, and deaths. These descriptive figures do not establish causation or comparative risk. The registry record does not report an analysis plan, primary endpoint precision, or the analysis population.